UVB induced reactivation leads to HSV1 in the corneas of virtually all latently infected mice and requires STING to develop corneal disease
Abstract Reactivation of latent herpes simplex type 1 results in virus returning to the cornea leading to recurrent herpetic stromal keratitis (rHSK). We compare two competing models to reactivate viruses from latency, UV-B irradiation and cyclophosphamide (CP). Results revealed that while both resu...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-03-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-52597-0 |
| _version_ | 1797247305691168768 |
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| author | Xiao-Tang Yin Alexis Hartman Nadia Sirajuddin Deepak Shukla Anthony St. Leger Tammie L. Keadle Patrick M. Stuart |
| author_facet | Xiao-Tang Yin Alexis Hartman Nadia Sirajuddin Deepak Shukla Anthony St. Leger Tammie L. Keadle Patrick M. Stuart |
| author_sort | Xiao-Tang Yin |
| collection | DOAJ |
| description | Abstract Reactivation of latent herpes simplex type 1 results in virus returning to the cornea leading to recurrent herpetic stromal keratitis (rHSK). We compare two competing models to reactivate viruses from latency, UV-B irradiation and cyclophosphamide (CP). Results revealed that while both result in corneal recrudescence, only UV-B irradiation results in rHSK. To better understand the dynamics of reactivation, we analyzed corneas for both the presence of infectious viruses and the dynamics of exposure to multiple reactivations using UV-B. We noted that multiple reactivations result in progressively worse corneal disease. We also noted that expression of IFNα and STING, surragate markers for the presence of virus, are induced by the presence of reactivated virus. Studies to determine the importance of STING to the development of HSK revealed that in the absence of STING, mice do not develop significant HSK and the magnitude of the infiltrate of CD45+ cells in these corneas is significantly reduced. The resulting paucity of CD45+CD11b+GR-1+F4/80-neutrophils, and to a lesser extent CD45+CD11b+GR-1-F4/80+ macrophages in B6-STING KO mice following reactivation is likely the underlying cause for lack of rHSK as has been noted by ourselves and others. These results underscore the critical importance of STING’s role in developing rHSK. |
| first_indexed | 2024-04-24T19:56:35Z |
| format | Article |
| id | doaj.art-f1ec81674d424adba6b32ee87a214526 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-24T19:56:35Z |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-f1ec81674d424adba6b32ee87a2145262024-03-24T12:21:20ZengNature PortfolioScientific Reports2045-23222024-03-0114111310.1038/s41598-024-52597-0UVB induced reactivation leads to HSV1 in the corneas of virtually all latently infected mice and requires STING to develop corneal diseaseXiao-Tang Yin0Alexis Hartman1Nadia Sirajuddin2Deepak Shukla3Anthony St. Leger4Tammie L. Keadle5Patrick M. Stuart6Department of Ophthalmology, Saint Louis University School of MedicineDepartment of Ophthalmology, Saint Louis University School of MedicineDepartment of Ophthalmology, Saint Louis University School of MedicineDepartment of Ophthalmology & Visual Sciences, University of Illinois at ChicagoDepartment of Ophthalmology, University of PittsburghDepartment of Biology, Washington UniversityDepartment of Ophthalmology, Saint Louis University School of MedicineAbstract Reactivation of latent herpes simplex type 1 results in virus returning to the cornea leading to recurrent herpetic stromal keratitis (rHSK). We compare two competing models to reactivate viruses from latency, UV-B irradiation and cyclophosphamide (CP). Results revealed that while both result in corneal recrudescence, only UV-B irradiation results in rHSK. To better understand the dynamics of reactivation, we analyzed corneas for both the presence of infectious viruses and the dynamics of exposure to multiple reactivations using UV-B. We noted that multiple reactivations result in progressively worse corneal disease. We also noted that expression of IFNα and STING, surragate markers for the presence of virus, are induced by the presence of reactivated virus. Studies to determine the importance of STING to the development of HSK revealed that in the absence of STING, mice do not develop significant HSK and the magnitude of the infiltrate of CD45+ cells in these corneas is significantly reduced. The resulting paucity of CD45+CD11b+GR-1+F4/80-neutrophils, and to a lesser extent CD45+CD11b+GR-1-F4/80+ macrophages in B6-STING KO mice following reactivation is likely the underlying cause for lack of rHSK as has been noted by ourselves and others. These results underscore the critical importance of STING’s role in developing rHSK.https://doi.org/10.1038/s41598-024-52597-0 |
| spellingShingle | Xiao-Tang Yin Alexis Hartman Nadia Sirajuddin Deepak Shukla Anthony St. Leger Tammie L. Keadle Patrick M. Stuart UVB induced reactivation leads to HSV1 in the corneas of virtually all latently infected mice and requires STING to develop corneal disease Scientific Reports |
| title | UVB induced reactivation leads to HSV1 in the corneas of virtually all latently infected mice and requires STING to develop corneal disease |
| title_full | UVB induced reactivation leads to HSV1 in the corneas of virtually all latently infected mice and requires STING to develop corneal disease |
| title_fullStr | UVB induced reactivation leads to HSV1 in the corneas of virtually all latently infected mice and requires STING to develop corneal disease |
| title_full_unstemmed | UVB induced reactivation leads to HSV1 in the corneas of virtually all latently infected mice and requires STING to develop corneal disease |
| title_short | UVB induced reactivation leads to HSV1 in the corneas of virtually all latently infected mice and requires STING to develop corneal disease |
| title_sort | uvb induced reactivation leads to hsv1 in the corneas of virtually all latently infected mice and requires sting to develop corneal disease |
| url | https://doi.org/10.1038/s41598-024-52597-0 |
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